Lucan · Conditions

Hyponatraemia

Australian guidance: Therapeutic Guidelines (eTG) kidney and urinary: Hyponatraemia in adults

1. Definition and epidemiology

Hyponatraemia is defined by the captured eTG topic as a serum sodium concentration less than 135 mmol/L, against a normal range of 135 to 145 mmol/L. Severity is classified as mild at 130 to less than 135 mmol/L, moderate at 120 to 129 mmol/L and severe at less than 120 mmol/L. Acuity is defined separately: acute hyponatraemia develops over less than 48 hours, and chronic hyponatraemia over 48 hours or more, with chronic hyponatraemia generally better tolerated.

The topic describes hyponatraemia as complex and often multifactorial, and notes that in most cases it reflects an excess of water rather than depletion of sodium, usually because renal water excretion is impaired by an inability to suppress antidiuretic hormone secretion. Many patients have a single cause, but multiple factors can contribute, for example a thiazide diuretic causing both syndrome of inappropriate antidiuretic hormone secretion and hypovolaemia.

The captured topic does not carry a prevalence or incidence figure for hyponatraemia in the community, in hospital inpatients or in any subgroup, so no numerical epidemiology is given here.

2. Pathophysiology

Hyponatraemia lowers serum tonicity, which promotes water movement into the brain. In acute or severe symptomatic hyponatraemia this creates the risk of cerebral oedema, and faster correction may be needed to restore tonicity. In chronic hyponatraemia the brain adapts by extruding solutes from the cytoplasm so that intracellular tonicity matches plasma tonicity and cerebral volume normalises.

That adaptation is why chronic hyponatraemia is corrected slowly: the brain cannot re-adapt if serum tonicity rises rapidly, and rapid correction may induce osmotic demyelination syndrome. Where intracranial pathology such as a brain tumour or subarachnoid haemorrhage is present, tolerance of cerebral swelling is reduced because intracranial pressure is already raised, and the immediate danger of cerebral oedema and brain herniation outweighs the risk of osmotic demyelination syndrome, so more rapid initial correction is warranted.

The captured text does not carry the osmoreceptor mechanism, the diagnostic criteria for syndrome of inappropriate antidiuretic hormone secretion, or an interpretation of antidiuretic hormone or blood copeptin concentrations.

3. Clinical presentation and diagnostic criteria

Mild hyponatraemia is usually asymptomatic. The risk and severity of symptoms are greater in acute than in chronic hyponatraemia and greater with increasing severity. Common symptoms are vomiting, nausea, fatigue, confusion, headache, dizziness, gait disturbance and cramps. Severe symptoms are seizures, altered conscious state, and cardiorespiratory distress or arrest.

Severe symptoms are rare in mild to moderate hyponatraemia, and if they are present an alternative explanation should be sought; if none is found, management follows the pathway for severe hyponatraemia with severe symptoms or intracranial pathology.

The diagnostic criteria are a confirmed serum sodium concentration below 135 mmol/L, classified by severity and by acuity. Confirmation requires repeat measurement, particularly in asymptomatic patients with no obvious cause; in extreme hyperlipidaemia or hyperproteinaemia the repeat should use direct ion-selective electrodes, because flame photometry can produce a falsely low result. Serum glucose must also be measured, because marked hyperglycaemia can produce a falsely low sodium concentration, and if glucose is greater than 12 mmol/L the sodium should be corrected for hyperglycaemia.

Once confirmed, paired serum and urine osmolality and paired serum and urine sodium concentrations are used to differentiate causes, with additional tests depending on the clinical circumstances. The captured topic does not reproduce Figure 23.16, so its branch-by-branch classification of causes is not carried, and it does not set out formal diagnostic criteria for syndrome of inappropriate antidiuretic hormone secretion or a volume-status algorithm in the text.

4. Investigations and AU-specific cutoffs

The reference interval of 135 to 145 mmol/L is the Australian harmonised chemical pathology interval, cited by eTG to the Royal College of Pathologists of Australasia, and all thresholds are in mmol/L. Serum osmolality is classified as low below 275 mOsm/kg, normal from 275 to 295 mOsm/kg and high above 295 mOsm/kg. Urine sodium is high above 40 mmol/L and low below 20 mmol/L, and urine osmolality is high above 300 mOsm/kg and low below 100 mOsm/kg.

The first step is confirmation: repeat the serum sodium, using direct ion-selective electrodes when extreme hyperlipidaemia or hyperproteinaemia is present, and measure serum glucose, correcting the sodium if glucose exceeds 12 mmol/L. The topic directs clinicians to the MD+CALC sodium correction for hyperglycaemia calculator for that correction but does not reproduce the formula, so no correction factor is given here.

Paired serum and urine osmolality and paired serum and urine sodium are then measured simultaneously. For euvolaemic hyponatraemia, thyroid function tests and serum cortisol can point to a cause; for hypervolaemic hyponatraemia, liver biochemistry, transthoracic echocardiography and urine albumin to creatinine ratio can be useful. The topic notes that antidiuretic hormone and blood copeptin are rarely measured because the result is unlikely to change management, and that urine sodium is often elevated in hyponatraemia associated with glucosuria, as in suboptimally managed diabetes, although it may vary with the stage of illness.

The clinical history should cover symptoms, endocrine, heart, liver and kidney disease, lung cancer, concurrent acute illness, fluid intake and losses, prescribed and non-prescribed medications, alcohol use, and recent surgery, especially neurosurgery, urological surgery or thoracic surgery. Examination should assess weight change, lying and standing blood pressure, urine output, peripheral oedema, jugular venous pressure, pulse rate, skin turgor and hydration of mucous membranes.

The captured topic does not carry the contents of Figure 23.16, a cortisol or thyroid function cutoff, or a formula for the hyperglycaemia correction.

5. Management

Moderate to severe hyponatraemia that is acute or symptomatic should be managed in hospital, while chronic hyponatraemia can often be managed in the community when it is mild and without severe symptoms. Initial management is identification and removal of precipitating factors, restoration of sodium and water balance, and minimisation of electrolyte-free water intake, with regular monitoring of serum electrolytes and urine output.

The rate of correction depends on acuity, the presence of severe symptoms and the risk of osmotic demyelination syndrome. If it is unclear whether hyponatraemia is acute or chronic, correction should follow the rate recommended for chronic hyponatraemia.

For chronic hyponatraemia without severe symptoms, without risk factors for osmotic demyelination syndrome and without intracranial pathology, serum sodium should rise by no more than 1 mmol/L every 2 hours and no more than 8 mmol/L every 24 hours. When risk factors for osmotic demyelination syndrome are present, the 24-hour ceiling falls to 6 mmol/L, while the 2-hourly ceiling remains 1 mmol/L. The risk factors listed are a serum sodium concentration of 105 mmol/L or less, concurrent hypokalaemia, a disorder of alcohol use, malnutrition and advanced liver disease.

For chronic hyponatraemia with severe symptoms or intracranial pathology, the initial target is a rise of 4 to 6 mmol/L within the first 1 to 2 hours, after which the rate is restricted to 1 mmol/L every 2 hours and 8 mmol/L every 24 hours. In acute hyponatraemia with severe symptoms or intracranial pathology the same initial rise of 4 to 6 mmol/L within 1 to 2 hours applies, but the subsequent rate does not need to be restricted; in acute hyponatraemia without severe symptoms or intracranial pathology the rate also does not need to be restricted.

For mild to moderate hyponatraemia, defined as 120 to 134 mmol/L without severe symptoms, a stable and asymptomatic mild case may need only intermittent monitoring, for example every 3 to 6 months. In euvolaemia or hypervolaemia, sodium is corrected by limiting 24-hour fluid intake to between 500 mL and 1 L, or to 500 mL less than the daily urine output. A loop diuretic may be required for oedema due to heart, liver or kidney failure when intravascular volume is not depleted, starting at a low dose such as furosemide 20 to 40 mg daily with slow adjustment.

In hypovolaemia, sodium is corrected with an intravenous infusion of sodium chloride 0.9%, at no faster than the rates in the correction table, with the initial rate calculated from the formula in Figure 23.18: the volume required over 24 hours equals the target minus the initial serum sodium concentration, multiplied by total body water, divided by the sodium content of the fluid. Total body water is estimated as bodyweight times 0.5 in females and times 0.6 in males.

Monitoring frequency in mild to moderate hyponatraemia is daily or every second day initially for mild cases, daily or twice daily for most moderate cases, and every 6 to 8 hours when more frequent measurement is needed to avoid rapid correction.

Tolvaptan is reserved for euvolaemic hyponatraemia that does not respond to fluid restriction; it is an orally administered vasopressin receptor antagonist registered in Australia for clinically significant euvolaemic hyponatraemia, defined as a serum sodium concentration less than 125 mmol/L or symptomatic hyponatraemia that does not resolve with fluid restriction, and it should be started only in hospital under specialist supervision with careful titration and close monitoring.

Severe hyponatraemia is often managed in a high-dependency environment, with serum sodium checked every 4 to 6 hours and every 1 to 2 hours when the cause is rapidly reversible, when severe symptoms are present, or when risk factors for osmotic demyelination syndrome are present. Adequate potassium replacement in hypokalaemia may reduce the risk of osmotic demyelination syndrome.

For severe hyponatraemia with severe symptoms or intracranial pathology, sodium chloride 3% 100 mL is given intravenously over 10 minutes, the serum sodium is rechecked after 20 to 30 minutes, and the dose may be repeated up to two more times if severe symptoms persist, aiming for an initial rise of 4 to 6 mmol/L within 1 to 2 hours. When that initial target is achieved, subsequent treatment follows the pathway for severe hyponatraemia without severe symptoms or intracranial pathology.

For severe hyponatraemia without severe symptoms or intracranial pathology, management follows the mild to moderate pathway with more frequent monitoring, and if the sodium does not rise, an intravenous infusion of sodium chloride 3% is started with an initial target of 120 mmol/L. The infusion rate must be calculated by an experienced clinician using the formula in Figure 23.19, in which the expected rise per litre equals 513 minus the measured serum sodium concentration, divided by total body water plus one. In the worked example, a 60 kg woman with a serum sodium of 110 mmol/L has a total body water of 30 kg, an expected rise of 13 mmol/L per litre, and requires 615 mL over 24 hours, or 25 mL per hour, to achieve an 8 mmol/L rise. If two 100 mL boluses have already been given, the remaining 415 mL over 24 hours is infused at 17 mL per hour.

6. Pharmacology and AU PBS notes

Tolvaptan is the only specific drug therapy described for euvolaemic hyponatraemia, and it is an orally administered vasopressin receptor antagonist registered in Australia for clinically significant euvolaemic hyponatraemia, meaning a serum sodium concentration less than 125 mmol/L or symptomatic hyponatraemia that does not resolve with fluid restriction. It requires careful dose titration and close monitoring, and should be initiated only in hospital under specialist supervision; the captured topic does not carry a starting dose, titration schedule or maximum dose, so none is given here.

Furosemide is used at a low dose of 20 to 40 mg daily when oedema from heart, liver or kidney failure is present without depleted intravascular volume, with slow dose adjustment because the effect on salt and water excretion is unpredictable.

Sodium chloride 0.9% is the intravenous fluid for hypovolaemic hyponatraemia, and sodium chloride 3% is reserved for severe hyponatraemia that has not responded to more conservative strategies, with the rate calculated by an experienced clinician. The captured topic does not carry PBS listing status, restriction codes, brand names, pack sizes or prices for tolvaptan, furosemide or either sodium chloride concentration, and the only regulatory status it states is that tolvaptan is registered in Australia.

7. Complications and monitoring

Rapid correction of chronic hyponatraemia may induce osmotic demyelination syndrome, a severe neurological condition caused by rapid changes in plasma osmolality that damages the myelin sheath protecting brain cells. Its features vary between individuals and may include encephalopathy, dysarthria, dysphagia, oculomotor abnormalities and quadriparesis. The risk is increased by a serum sodium concentration of 105 mmol/L or less, concurrent hypokalaemia, a disorder of alcohol use, malnutrition and advanced liver disease.

Uncorrected hyponatraemia can cause seizures, altered conscious state, and cardiorespiratory distress or arrest, and the risk is greater in acute hyponatraemia and with increasing severity. In acute hyponatraemia, low serum tonicity promotes water movement into the brain and cerebral oedema, which is why faster correction may be necessary. In intracranial pathology, cerebral oedema and brain herniation are the immediate dangers.

Monitoring in severe hyponatraemia is every 4 to 6 hours, and every 1 to 2 hours when the cause is rapidly reversible, severe symptoms are present, or osmotic demyelination risk factors are present. In mild to moderate hyponatraemia, monitoring is daily or every second day for mild cases, daily or twice daily for most moderate cases, and every 6 to 8 hours when rapid correction is a concern. Ensuring adequate potassium replacement when hypokalaemia coexists may reduce the risk of osmotic demyelination syndrome.

The captured topic does not carry a mortality rate for hyponatraemia, a duration for monitoring after correction is complete, or a desmopressin relowering protocol for overcorrection.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.